Citation: Yin Wang, Hai-bo Wang, Hai-jie Han, Fan Jia, Qiao Jin, Jian Ji. Construction of Multifunctional Drug Nanocarriers by Modularized Host-Guest Self-assembly[J]. Acta Polymerica Sinica, ;2018, 0(8): 1089-1096. doi: 10.11777/j.issn1000-3304.2018.18035 shu

Construction of Multifunctional Drug Nanocarriers by Modularized Host-Guest Self-assembly

Ministry of Education Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027

Corresponding author: Jian Ji, jijian@zju.edu.cn
Received Date: 1 February 2018
Revised Date: 12 February 2018
Available Online: 13 April 2018

Unlike the crude study conducted at the beginning of nanomedicine, researchers have devoted more efforts to developing nanosystems with elaborated structures and multifunctions owing to the fact that the tumor microenvironment is complicated. However, it is still a great challenge to prepare these nanoplatforms for drug delivery. In this study, multifunctional prodrug nanocarriers were fabricated by the modularized host-guest self-assembly between cholesterol and β-cyclodextrin. The targeted ligand lactobionic acid (LBA), fluorescent probe fluoresceine isothiocyanate (FITC), and chemtherapeutic drug doxorubicin (DOX) were integrated into the multifunctional supramolecualr drug nanocarriers. The host-guest interaction between Chol-PEG and β-CD-hydrazone-DOX was confirmed by 2D ¹H NOESY spectrum. The modularized functional building blocks could self-assemble into micelles with a diameter of 20 nm. The supramolecular nanocarriers showed pH-sensitive drug release behavior. The release of DOX can be greatly accelerated in acidic endo/lysosomal pH. The internalization of the supramolecular drug nanocarriers by HepG2 cells was studied by fluorescence microscopy and flow cytometry. The nanocarriers can be well taken up by cancer cells. Due to the targeting ability of LBA, the internalization of the nanocarriers can be greatly inhibited if the cells are pre-treated by free LBA. At the same time, the fluorescence of FITC can be clearly observed intracellularly, which can be used to track the sub-cellular location of the drug nanocarriers. Finally, the cytotoxicity of the drug nanocarriers was investigaed by MTT assay. With the HepG2 cells pre-treated with free LBA, the cytotoxicity of the drug nanocarriers was significantly reduced, most probably owing to the unsatisfactory cell uptake. The concentration-dependent cytotoxicity toward HepG2 cells was also observed. Therefore, the integration of target ligand and imaging ligand have endowed the nanocarriers with targeted theranostic property. More importantly, since the modularized host-guest self-assembly is dynamically tunable, the percentage of functional ligands could be easily optimized to achieve a better outcome. Such multifunctional prodrug nanocarriers fabricated by modularized host-guest self-assembly may have great potential in drug delivery.
- Host-guest interactions,
- Supramolecule,
- Drug delivery,
- Imaging
1. [1]
  Hare J I, Lammers T, Ashford M B, Puri S, Storm G, Barry S T. Adv Drug Deliv Rev, 2017, 108(25-38 doi: 10.1016/j.addr.2016.04.025
2. [2]
  Allen T M, Cullis P R. Adv Drug Deliv Rev, 2013, 65(1): 36-48 doi: 10.1016/j.addr.2012.09.037
3. [3]
  Peer D, Karp J M, Hong S, FaroKHzad O C, Margalit R, Langer R. Nat Nanotechnol, 2007, 2(12): 751-760 doi: 10.1038/nnano.2007.387
4. [4]
  Duncan R. Nat Rev Cancer, 2006, 6(9): 688-701 doi: 10.1038/nrc1958
5. [5]
  Xie L S, Wang G H, Zhou H, Zhang F, Guo Z D, Liu C, Zhang X Z, Zhu L. Biomaterials, 2016, 103(219-228 doi: 10.1016/j.biomaterials.2016.06.058
6. [6]
  Han H J, Valdeperez D, Jin Q, Yang B, Li Z H, Wu Y L, Pelaz B, Parak W J, Ji J. ACS Nano, 2017, 11(2): 1281-1291 doi: 10.1021/acsnano.6b05541
7. [7]
  Liong M, Lu J, Kovochich M, Xia T, Ruehm S G, Nel A E, Tamanoi F, Zink J I. ACS Nano, 2008, 2(5): 889-896 doi: 10.1021/nn800072t
8. [8]
  Zhou Z J, Wang Y T, Yan Y, Zhang Q, Cheng Y Y. ACS Nano, 2016, 10(4): 4863-4872 doi: 10.1021/acsnano.6b02058
9. [9]
  Chen W H, Lei Q, Luo G F, Jia H Z, Hong S, Liu Y X, Cheng Y J, Zhang X Z. ACS Appl Mater Interfaces, 2015, 7(31): 17171-17180 doi: 10.1021/acsami.5b04031
10. [10]
  Fu P P, Xia Q S, Hwang H M, Ray P C, Yu H T. J Food Drug Anal, 2014, 22(1): 64-75 doi: 10.1016/j.jfda.2014.01.005
11. [11]
  Wang S Y, Kim G, Lee Y E K, Hah H J, Ethirajan M, Pandey R K, Kopelman R. ACS Nano, 2012, 6(8): 6843-6851 doi: 10.1021/nn301633m
12. [12]
  Chen Y J, Li Z H, Wang H B, Wang Y, Han H J, Jin Q, Ji J. ACS Appl Mater Interfaces, 2016, 8(11): 6852-6858 doi: 10.1021/acsami.6b00251
13. [13]
  Han H J, Wang H B, Chen Y J, Li Z H, Wang Y, Jin Q, Ji J. Nanoscale, 2016, 8(1): 283-291 doi: 10.1039/C5NR06734K
14. [14]
  Yang B, Dong X, Lei Q, Zhuo R X, Feng J, Zhang X Z. ACS Appl Mater Interfaces, 2015, 7(39): 22084-22094 doi: 10.1021/acsami.5b07549
15. [15]
  Liu J, Tan C S Y, Yu Z Y, Lan Y, Abell C, Scherman O A. Adv Mater, 2017, 29(10): 1604951 DOI: 10.1002/adma.201604951 doi: 10.1002/adma.201604951
16. [16]
  Liu J, Lan Y, Yu Z Y, Tan C S Y, Parker R M, Abell C, Scherman O A. Acc Chem Res, 2017, 50(2): 208-217 doi: 10.1021/acs.accounts.6b00429
17. [17]
  Zhou J, Yu G C, Huang F H. Chem Soc Rev, 2017, 46(22): 7021-7053 doi: 10.1039/C6CS00898D
18. [18]
  Yu G C, Jie K C, Huang F H. Chem Rev, 2015, 115(15): 7240-7303 doi: 10.1021/cr5005315
19. [19]
  Liu G Y, Jin Q A, Liu X S, Lv L P, Chen C J, Ji J A. Soft Matter, 2011, 7(2): 662-669 doi: 10.1039/C0SM00708K
20. [20]
  Wang Y, Wang H B, Chen Y J, Liu X S, Jin Q, Ji J. Chem Commun, 2013, 49(64): 7123-7125 doi: 10.1039/c3cc43687j
21. [21]
  Wang Y, Wang H B, Chen Y J, Liu X S, Jin Q, Ji J. Colloid Surf B-Biointerfaces, 2014, 121: 189-195 doi: 10.1016/j.colsurfb.2014.06.024
22. [22]
  Wang Y, Wang H B, Liu G Y, Liu X S, Jin Q, Ji J. Macromol Biosci, 2013, 13(8): 1084-1091 doi: 10.1002/mabi.201300052
23. [23]
  van de Manakker F, van der Pot M, Vermonden T, van Nostrum C F, Hennink W E. Macromolecules, 2008, 41(5): 1766-1773 doi: 10.1021/ma702607r
24. [24]
  Jiang H M, Zhang S F, Sui Q. Asian J Chem, 2011, 23(9): 3783-3786
25. [25]
  Ringsdorf H. J Polym Sci Polym Symp, 1975, 51: 135-153
26. [26]
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